Conventionally, concerning an administration method of medicine, the oral administration method using a tablet, a capsule, a syrup or the like has been known. However; in these years, an approach is tried in which these medicines are transdermally administrated by using a patch. The administration method using a patch can dissolve problems in the oral administration method and, in addition, has such advantages as decrease of administration frequency, enhancement of compliance, easiness of administration and discontinuation thereof. Therefore, it is expected as a useful administration method especially for the case where patients are aged persons or children.
However, the stratum corneum of the normal skin has a barrier function of inhibiting exogenous materials from penetrating into the body. Due to the barrier function, compounded medicinal ingredients often do not be transdermally absorbed sufficiently when conventional patches are used. Further, since the stratum corneum has a high lipid solubility, generally skin permeability of a medicine is extremely low.
Therefore, in order to enhance a transdermal absorption property of a medicine in the transdermal administration method, studies have been proceeded about composition and the like of an adhesive agent for use in a patch. As a part of them, such a patch is proposed that uses polymer material such as acrylic polymer or rubber polymer as an adhesive agent (JP-A-4-266821, JP-A-9-301854 and the like). Disclosure of the Invention
However, when the aforementioned conventional patches are used, it can not necessarily be said that skin permeability of a medicine is sufficient. In addition, in these conventional patches, due to a fact that physical property of the formula such as cohesive and adhesive property of the adhesive layer is degraded when a transdermal absorption property of a medicine is enhanced, it is very difficult to satisfy all the characteristic features required as a patch. Further, property of medicines for use in a patch varies depending on kinds thereof and, on the other hand, compatibility of an adhesive agent to a specified medicine is not examined sufficiently yet.
The present invention was achieved in consideration of the problems included in the aforementioned conventional technique, and the object of the invention is to provide a patch employing oxybutynin and/or a pharmaceutically acceptable salt thereof as a medicine, wherein the patch can achieve both of a skin absorption property of the medicine and physical property of the formula at a high level.
The present inventors made efforts to achieve the aforementioned object, and found that many of acrylic polymer among polymer materials used in the conventional patch have a carboxyl group (—COOH) or a hydroxyl group (—OH) in the molecule as a reaction point for crosslinking, and that it is very difficult to make both of a skin absorption property of a medicine and physical property of the formula compatible. And, as the result of further efforts based on the knowledge, we found that the aforementioned problems can be dissolved by incorporating an acrylic polymer substantially free of both carboxyl group and hydroxyl group and rubber polymer in an adhesive layer at a specified ratio respectively in a patch employing oxybutynin and/or a pharmaceutically acceptable salt thereof as a medicine, to accomplish the invention.
Thus, the patch of the invention is a patch comprising a backing layer and an adhesive layer disposed on the backing layer and compounded with an adhesive agent and oxybutynin and/or a pharmaceutically acceptable salt thereof, wherein the adhesive agent comprises an acrylic polymer substantially free of both carboxyl group and hydroxyl group and rubber polymer at a weight ratio of content of the acrylic polymer to content of the rubber polymer of from 1:4 to 1:19.
In the invention, preferably the adhesive layer comprises 0.5-10% by weight of the acrylic polymer, 5-40% by weight of the rubber polymer and 10-60% by weight of an alicyclic saturated hydrocarbon resin-based tackifier on the basis of the total amount of compounds contained in the adhesive layer.
Further, in the invention, preferably a weight ratio of the total content of the acrylic polymer and the rubber polymer to content of the tackifier is from 1:1 to 1:3.
Further, in the invention, it is preferable that the acrylic polymer is at least one kind selected from: copolymer of polyacrylate including at least one selected from 2-ethylhexyl acrylate, butyl acrylate, diacetone acrylamide and tetraethylene glycol dimethacrylate, and polymethyl methacrylate; 2-ethylhexyl acrylate-N-vinyl-2-pyrrolidone-1,6-hexane glycol dimethacrylate terpolymer; aminoalkyl methacrylate copolymer E; and 2-ethylhexyl acrylate-vinyl acetate copolymer.
Further, in the invention, it is preferable that the rubber polymer is at least one kind selected from styrene-isoprene-styrene block copolymer, styrene-butadiene-styrene block copolymer, styrene-butadiene rubber, polyisobutylene, isoprene rubber and silicone rubber.
Furthermore, in the invention, preferably the rubber polymer is at least one kind selected from styrene-isoprene-styrene block copolymer and polyisobutylene.
Furthermore, in the invention, it is preferable that the acrylic polymer is at least one kind selected from 2-ethylhexyl acrylate-N-vinyl-2-pyrrolidone-1,6-hexane glycol dimethacrylate terpolymer and 2-ethylhexyl acrylate-vinyl acetate copolymer; and that the rubber polymer is styrene-isoprene-styrene block copolymer.
Still furthermore, in the invention, preferably a oxybutynin hydrochloride is compounded in the adhesive layer.
Still furthermore, in the invention, preferably the adhesive agent further comprises an organic acid, more preferably the organic acid is at least one kind selected from acetic acid and citric acid, and salts of these acids.